Research Topics
| S EnglanderSummaryAffiliation: University of Pennsylvania Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Protein folding and misfolding: mechanism and principlesS Walter Englander
The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia 19104 6059, USA
Q Rev Biophys 40:287-326. 2007..Cooperative native-like foldon units and the sequential stabilization process together generate predetermined stepwise pathways. Optional misfolding errors are responsible for 3-state and heterogeneous kinetic folding...
How cytochrome c folds, and why: submolecular foldon units and their stepwise sequential stabilizationHaripada Maity
Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
J Mol Biol 343:223-33. 2004..Much related information for Cyt c strongly conforms with this mechanism. Its generality is supported by available information for other proteins...- Protein structure change studied by hydrogen-deuterium exchange, functional labeling, and mass spectrometryJoan J Englander
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 100:7057-62. 2003..Allosterically sensitive amide hydrogens located at near amino acid resolution help to confirm the reality of local unfolding reactions and their use to evaluate resolved structure changes in terms of allosteric free energy... - Cytochrome c folding pathway: kinetic native-state hydrogen exchangeLinh Hoang
The Johnson Research Foundation, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
Proc Natl Acad Sci U S A 99:12173-8. 2002..Four distinct unfolding steps are found to be kinetically ordered in the same pathway sequence inferred before... - Protein folding: the stepwise assembly of foldon unitsHaripada Maity
Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
Proc Natl Acad Sci U S A 102:4741-6. 2005..Four other proteins have been found to show similar behavior. These results support stepwise protein folding pathways through discrete intermediates... - Functional role of a protein foldon--an Omega-loop foldon controls the alkaline transition in ferricytochrome cHaripada Maity
The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Proteins 63:349-55. 2006..In addition, the results obtained confirm the epsilon-amino group of Lys79 and Lys73 as the alkaline replacement ligands and bear on the search for a triggering group... - Order of steps in the cytochrome C folding pathway: evidence for a sequential stabilization mechanismMallela M G Krishna
Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, 19104 6059, USA
J Mol Biol 359:1410-9. 2006..Where the native structure of Cyt c requires sequential folding, in the first three steps, this is found. Where structural determination is ambiguous, in the final two steps, alternative parallel folding is found... - A unified mechanism for protein folding: predetermined pathways with optional errorsMallela M G Krishna
Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6059, USA
Protein Sci 16:449-64. 2007..The integration of three well-documented principles in the PPOE model (cooperative foldons, sequential stabilization, optional errors) provides a unifying explanation for how proteins fold and why they fold in that way... - Branching in the sequential folding pathway of cytochrome cMallela M G Krishna
Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6059, USA
Protein Sci 16:1946-56. 2007.... - The foldon substructure of staphylococcal nucleaseSabrina Bedard
Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
J Mol Biol 376:1142-54. 2008..Because the unfolding parameters of many other residues are not determined, it seems likely that the concerted foldon units are more extensive than is shown by the 34 residues actually observed... - Protein folding: independent unrelated pathways or predetermined pathway with optional errorsSabrina Bedard
Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 105:7182-7. 2008..Structural, kinetic, and thermodynamic information for the folding intermediates and pathways of many proteins is consistent with the predetermined pathway-optional error (PPOE) model but contrary to the properties implied in IUP models... - Urea, but not guanidinium, destabilizes proteins by forming hydrogen bonds to the peptide groupWoon Ki Lim
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 106:2595-600. 2009..Results for guanidinium, however, are contrary to the expectation that it might H-bond. Evidently, urea and guanidinium, although structurally similar, denature proteins by different mechanisms... - The N-terminal to C-terminal motif in protein folding and functionMallela M G Krishna
Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
Proc Natl Acad Sci U S A 102:1053-8. 2005..Possible reasons for this bias relate to the mechanisms for initial protein folding, native state stability, and final turnover... - Fast structural dynamics in reduced and oxidized cytochrome cWeixia Liu
Department of Biochemistry and Biophysics, Johnson Research Foundation, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6059, USA
Protein Sci 18:670-4. 2009..The relative rigidity of both redox states also implies that dynamic relief of destructive electron transfer pathway interference is not operational in free cytochrome c... - Recombinant equine cytochrome c in Escherichia coli: high-level expression, characterization, and folding and assembly mutantsJon N Rumbley
The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6059, USA
Biochemistry 41:13894-901. 2002..In addition, destabilizing glycine mutants in the N-terminal helix are shown to affect the fractional yield of a heme inverted Cyt c isoform... - Submolecular cooperativity produces multi-state protein unfolding and refoldingS Walter Englander
Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
Biophys Chem 101:57-65. 2002..Folding uses the same pathway in the reverse direction, moving from the unfolded to the native state through relatively discrete intermediate forms by the sequential addition of native-like secondary structural units... - Protein hydrogen exchange mechanism: local fluctuationsHaripada Maity
The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Protein Sci 12:153-60. 2003..In both modes, ionic hydrogen exchange catalysts attack from the bulk solvent without diffusing through the protein matrix... - Cooperative omega loops in cytochrome c: role in folding and functionMallela M G Krishna
Department of Biochemistry and Biophysics, Johnson Research Foundation, University of Pennsylvania School of Medicine, 422 Curie Blvd, 1007 Stellar Chance Bldg, Philadelphia, PA 19104 6059, USA
J Mol Biol 331:29-36. 2003..This unit behavior accounts for an initial step on the unfolding pathway, a final step in refolding, and a number of other structural, functional and evolutionary properties... - Folding units govern the cytochrome c alkaline transitionLinh Hoang
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
J Mol Biol 331:37-43. 2003..These and other results show that the cooperative folding-unfolding behavior of protein foldons can account for a variety of functional activities in addition to determining folding pathways... - Hydrogen exchange methods to study protein foldingMallela M G Krishna
Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
Methods 34:51-64. 2004..The results obtained in these ways suggest principles that appear to explain the properties of partially folded intermediates and how they are organized into folding pathways. The application of these methods is detailed here... - Backbone and side-chain heteronuclear resonance assignments and hyperfine NMR shifts in horse cytochrome cWeixia Liu
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Protein Sci 12:2104-8. 2003..The refined g-tensors were then used to probe for redox-dependent structure change in the two proteins... - Intimate view of a kinetic protein folding intermediate: residue-resolved structure, interactions, stability, folding and unfolding rates, homogeneityMallela M G Krishna
Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
J Mol Biol 334:501-13. 2003..The general problem of homogeneous versus heterogeneous intermediates and pathways is discussed... - Protein misfolding: optional barriers, misfolded intermediates, and pathway heterogeneityMallela M G Krishna
Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
J Mol Biol 343:1095-109. 2004..Related observations for other proteins (partially misfolded intermediates, pathway heterogeneity) might be similarly explained in terms of the optional insertion of error-dependent barriers into a classical folding pathway... - Hydrogen exchange and mass spectrometry: A historical perspectiveS Walter Englander
The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6059, USA
J Am Soc Mass Spectrom 17:1481-9. 2006..This article briefly reviews the advances that have led us to this point and the understanding that has so far been achieved... - The Mad2 partial unfolding model: regulating mitosis through Mad2 conformational switchingJohn J Skinner
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA
J Cell Biol 183:761-8. 2008..Recent structural, biochemical, and cell biological advances suggest that the catalyzed conversion of Mad2 requires a major structural rearrangement that transits through a partially unfolded intermediate... - Structure and properties of alpha-synuclein and other amyloids determined at the amino acid levelCharyl Del Mar
The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 102:15477-82. 2005..Seeding specificity, strain variability, and species barriers then arise because newly added parallel in-register chains must faithfully reproduce the same set of adaptations... - Fast and slow intermediate accumulation and the initial barrier mechanism in protein foldingBryan A Krantz
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA
J Mol Biol 324:359-71. 2002..Results available provide little support for early intermediate accumulation before an initial search-dependent nucleation barrier... - Folding trajectories of human dihydrofolate reductase inside the GroEL GroES chaperonin cavity and free in solutionReto Horst
Department of Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 104:20788-92. 2007.... - The E46K mutation in alpha-synuclein increases amyloid fibril formationEric A Greenbaum
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 280:7800-7. 2005..These findings support the notion that aberrant alpha-synuclein polymerization resulting in the formation of pathological inclusions can lead to disease...
Research Grants
- Hydrogen exchange, proteins, and foldingS Englander; Fiscal Year: 2005..An approach will be attempted that promises to make the native state HX method generally applicable to the majority of proteins which have so far not been accessible to this analysis. Other work is planned. ..
- Hydrogen exchange, proteins, folding, and misfoldingS Englander; Fiscal Year: 2007....
- Protein dynamics studies by hydrogen exchangeS Englander; Fiscal Year: 2007..To study the functional role of the dynamic dimension of protein structure, hydrogen exchange approaches will be applied to the study of enzymatic function. ..
- Hydrogen exchange, proteins, folding, and misfoldingS Englander; Fiscal Year: 2009..abstract_text> ..
- INTERMEDIATES AND THE BARRIERS IN PROTEIN FOLDINGS Englander; Fiscal Year: 2001..The experiments will use mammalian, bacterial, and genetically engineered versions of cytochrome c as model proteins, and other useful model proteins. ..
- FUNCTIONAL LABELING OF CYTOCHROME C BY H-EXCHANGE & NMRS Englander; Fiscal Year: 1993....
- Foldons, folding, and functionS Walter Englander; Fiscal Year: 2010....